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Biomedical subjects

G Greenberg

Publications and source records attributed to G Greenberg.

At least 37 records · Page 2Linked to original sources

Bone remodeling in W/Wv mast cell deficient mice.

Strong experimental evidence exists for a relationship between mast cells and bone disease, but the role of mast cells in the regulation of bone remodeling is unknown. In order to address this question, mast cell deficient mice (W/Wv) were paired with their mast cell sufficient (+/+) littermates and evaluated for differences in response to an induced cycle of bone remodeling. This was achieved using a tooth egression protocol, in which a synchronous cycle of bone remodeling was induced in the mandibular buccal alveolar periosteum by extraction of the opposing dentition. Quantitative histomorphometric changes during the activation, resorption, reversal, and formation phases of bone remodeling were documented using standard techniques. Most cell deficient mutants exhibited the following defects in response to an induced cycle of bone remodeling: (a) the onset of the remodeling cycle was delayed by a prolonged activation phase, (b) the duration and extent of the active formation phase was decreased, and (c) the amount of new bone matrix synthesized was diminished while mineralization rates were found to be normal. These results suggest that mast cells and their mediators provide a paracrine mechanism which influences the recruitment of osteoclast and osteoblast progenitors and their participation in bone remodeling. Nonetheless, since bone remodeling occurs in mast cell deficient mice, albeit less efficiently, this mechanism is most likely one of several redundant mechanisms that provide for adequate skeletal homeostasis.

Animals↗

Additive effects of psychostimulants, parent training, and self-control therapy with ADHD children.

Utilizing a double-blind, placebo design, the effects of a high (0.8 mg/kg) and a low (0.4 mg/kg) dose of methylphenidate alone and in combination with behavioral parent training plus child self-control instruction were evaluated with 96 attention deficit hyperactivity disorder children. No evidence of the superiority of the combined conditions relative to medication alone was found. Some limited support was found for the hypothesis that the effects of a high dose of psychostimulant medication could be achieved by combining the low dose with a behavioral intervention. The importance of the latter finding is highlighted by the fact that both the benefits and untoward effects of the psychostimulants appear to increase with the dose.

Attention Deficit Disorder with Hyperactivity↗

Risk factors for stroke and myocardial infarction in women in the United Kingdom as assessed in general practice: a case-control study.

Data available in the United Kingdom through the Medical Research Council's General Practice Research Framework were recorded in a study of 603 women aged 45-69 with confirmed diagnoses of stroke or myocardial infarction, each matched by age with two controls. Current cigarette smoking and a family history of myocardial infarction were both strongly associated with the risk of stroke and myocardial infarction, with relative risks of 2.47 (95% confidence interval 1.89 to 3.23) and 1.93 (95% confidence interval 1.52 to 2.44) respectively. The relative risks associated with past smoking decreased according to the length of time since stopping smoking. A family history of stroke was not significantly related to the risk of stroke or myocardial infarction. Single women had a lower risk of stroke and myocardial infarction than married women (relative risk 0.49), but parity, past use of oral contraceptives, and menopausal state were not significantly related to the risk of stroke and myocardial infarction in this study. Other characteristics that were identified as risk factors either for subsequent stroke or for myocardial infarction included not only hypertension, diabetes, and past histories of stroke and myocardial infarction, but also past histories of gynaecological cancer and of venous thrombosis. The association with venous thrombosis may indicate the importance of the haemostatic system in a common pathogenesis of venous thrombosis and myocardial infarction.

Aged↗

The use of hormonal replacement therapy and the risk of stroke and myocardial infarction in women.

STUDY OBJECTIVE: To determine whether there is an association between the use of hormonal replacement therapy (HRT) and the risk of stroke and myocardial infarction (MI). DESIGN: A case-control study of women with stroke or MI was undertaken. SETTING: The cases were notified from 83 general practices to the coordinating centre at Northwick Park Hospital, where the diagnoses were independently confirmed. SUBJECTS: The cases, 603 white women aged 45-69, were each matched to two controls for age and general practitioner. Of the controls, 79% were the first eligible, 15% the second eligible and 6% were obtained at the third or more attempt. MEASUREMENTS AND MAIN RESULTS: A research nurse completed a questionnaire for each case and both controls, which included information obtained from the medical notes on the prescriptions of HRT. An independent quality control check on the selection of controls and on the abstraction of information from the medical notes was made. More than one HRT prescription had been given to 109 cases (18%) and 174 controls (14%), showing a weak association between the risk of stroke and MI and the past use of HRT (relative risk [RR] 1.36, 95% confidence interval [CI] 1.01-1.81). There was a stronger association with preparations contained progestogen alone (RR 1.90, 95% CI 1.11-3.25). On average, HRT had been used 9 years before recruitment to the study and for 15 months. However, the observed gradients of risk according to the duration of HRT use and time since HRT use do not support a causal interpretation. Also, the estimated relative risks were reduced when allowance was made for other cardiovascular risk factors. CONCLUSIONS: There is no evidence that the use of HRT as recently prescribed in the UK constitutes a major cardiovascular risk or benefit.

Aged↗

Low glycemic index foods and reduced glucose, amino acid, and endocrine responses in cirrhosis.

Carbohydrate intolerance is common in patients with cirrhosis. The aim of the present study was to determine whether the beneficial metabolic effects of low glycemic index diets observed in noncirrhotic diabetics also occurred in patients with cirrhosis. Therefore, for one day, five patients with cirrhosis were fed diets in which low glycemic index foods were substituted, replacing those which produced higher blood glucose rises. Reduction in the estimated glycemic impact of the diet by approximately 30% reduced the mean incremental blood glucose level over the day by 40 +/- 5% (p less than 0.001). Measurement at breakfast of amino acid, insulin, and gastric inhibitory polypeptide profiles confirmed a reduction of similar magnitude. No change was seen in pancreatic glucagon, whereas enteroglucagon levels tended to be higher. In view of these findings and the possible long-term benefits of chronic reduction of hyperinsulinism and alteration in amino acid metabolism, this approach to dietary management of cirrhosis warrants further consideration.

Aged↗

The relationship between smoking and the response to anti-hypertensive treatment in mild hypertensives in the Medical Research Council's trial of treatment.

The antihypertensive efficacy of propranolol in the treatment of mild hypertension was significantly impaired in cigarette smokers, whereas that of bendrofluazide was not affected by smoking habit. This diminished efficacy of propranolol in smokers may be one of several possible factors operating to reduce its primary preventive action against strokes, and possibly against coronary events.

Adult↗

Relation between cigarette smoking and use of hormonal replacement therapy for menopausal symptoms.

The aim of this study was to characterise new users of hormonal replacement therapy (HRT) for the relief of menopausal symptoms and to compare these women with never-users of HRT; 402 new users and 804 never-users were studied. Hot flushes were the most common symptom in both users and non-users and were the most frequent reason for prescribing HRT. The prevalence of menopausal symptoms in non-users of HRT was high although substantially lower than that in users. HRT users were more likely to be current cigarette smokers than were never-users. There was also, within smokers, a significant relation between the number of cigarettes smoked and the likelihood of using HRT. This relation between HRT use and smoking could result from an anti-oestrogen effect of smoking, intensifying menopausal symptoms. Of potential clinical relevance is the suggestion that a proportion of women using HRT may be doing so in order to alleviate smoking-induced symptoms. Users of HRT were also more likely to have used oral contraceptives than were never-users; this relation was probably behavioural.

Climacteric↗

Leukotrienes C4 and D4 do not increase filtration coefficient of excised perfused guinea pig lungs.

We tested the direct effects of leukotriene (LT) C4 or D4 on the pulmonary vascular fluid filtration coefficient (Kf) by adding these LT's to the cell-depleted perfusate of excised guinea pig lungs. Pulmonary arterial (Ppa) and airway (Paw) pressures were monitored, and left atrial pressure was kept constant during 10 min of constant-flow perfusion. Kf's were then calculated by two methods [Drake and colleagues (KfD), Am. J. Physiol. 234 (Heart Circ. Physiol. 3): H266-H274, 1978; and Goldberg (KfG), Am. J. Physiol. 239 (Heart Circ. Physiol. 8): H189-H198, 1980] from the change in lung weight resulting from a no-flow zone 3 hydrostatic stress applied for 20 min. With no LT's (Tyrode's buffer alone), the mean +/- SE Paw was 9.0 +/- 0.7 cmH2O and the Ppa was 14.2 +/- 1.1 cmH2O throughout the 10-min perfusion. The KfD and KfG were 1.239 +/- 0.169 and 1.586 +/- 0.223 ml X min-1 X mmHg-1 X 100 g lung-1, respectively. The mean +/- SE lung wet-to-dry ratio (W/D) after the 20-min hydrostatic stress was 16.7 +/- 1.6. Within 30-45 s of adding 4 micrograms of LTC4 or LTD4, Paw and Ppa both increased and remained elevated throughout the perfusion period. The KfD and KfG were 1.586 +/- 0.223 and 2.071 +/- 0.234 ml X min-1 X mmHg-1 X 100 g lung-1, respectively, and the W/D was 18.1 +/- 1.7 after LTC4 (all P greater than 0.4 compared with Tyrode's buffer alone) and 1.417 +/- 0.200 and 1.851 +/- 0.244 ml X min-1 X mmHg-1 X 100 g lung-1, respectively, with a W/D of 20.5 +/- 1.3 after LTD4 (all P greater than 0.4 compared with Tyrode's buffer alone).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Further results of the MRC treatment trial for mild hypertension.

17,354 mildly hypertensive adults with diastolic (v) pressures of 90-109 mm Hg took part in a 5 1/2 year trial in which each was randomized to treatment with either bendrofluazide, propranolol, or placebo. The main results of the trial have been published; they showed stroke benefit but no overall reduction in the incidence of coronary events and no effect on all-cause mortality. Further analyses of the data have shown interesting differences between subgroups of the population, with regard to the effects of the two types of treatment on stroke, on coronary events and on ECG changes. These results, and the effects of interaction between cigarette smoking and the efficacy of these drugs, if confirmed in other studies, should influence the choice of drug therapy for mild hypertension.

Bendroflumethiazide↗

Depth perception in Mongolian gerbils (Meriones unguiculatus) and spiny mice (Acomys russatus and A. cahirinus).

Depth perception in gerbils and spiny mice was studied with a modified visual cliff which varied the height of a platform from 5.08 cm to 25.4 cm and presented animals with an apparent drop-off to a patterned or a white field. Time to descend from the platform and orienting response frequency were recorded. For gerbils neither measure varied significantly between the platforms. Both Acomys species increased descent time and orienting response frequency as platform height increased. The results suggest that both gerbils and spiny mice can perceive depth, though there appears to be a difference between the species' use of sensory cues in descending from a visual cliff. The spiny mice appear to rely more on visual cues than do the gerbils. The data also reveal subtle behavioral differences between the Acomys species that may relate to their successful sympatry. The results are discussed by alluding to ecological differences between these species in their natural habitats.

Animals↗

Inhibition of bone resorption in vitro by compound 48/80.

The mechanisms that control cycles of bone formation and bone resorption are not well understood. In this report we provide evidence that compound 48/80 is a potent inhibitor of bone resorption in vitro. Resorption was assessed by the release of calcium-45 from pre-labelled newborn mouse calvaria that were treated with compound 48/80 and/or parathyroid hormone (PTH) in organ culture. Our results demonstrate that co-incubation of calvaria with PTH plus compound 48/80 (concentrations 1-10 mcg/ml) produces a marked reduction of calcium-45 release compared to PTH alone. Furthermore, pre-incubation of calvaria with compound 48/80, for as little as three hours, inhibits resorption by subsequent treatment with PTH alone. Measurement of lactate dehydrogenase (LDH) released into the culture medium indicated that treatment with compound 48/80, at the doses and time periods studied, was not cytotoxic. This novel effect of compound 48/80 may provide a useful tool for studying the cellular mechanisms involved in the bone resorption process.

Animals↗

Blood pressure and the menstrual cycle.

A retrospective analysis of data from 207 non-pregnant premenopausal women showed that the mean level of systolic blood pressure varied with the stage of the menstrual cycle, being higher on days 17-26, the part of the luteal phase during which the peak of progestogen levels develops, than during the luteal phase as a whole, and significantly higher than the mean for all other days of the cycle. The mean levels were 125.4 mmHg (SE 1.76) for days 17-26, 122.5 (SE 1.25) for days 15-28 and 120.1 (SE 1.07) for days 1-16, 27 and 28. This finding supported the hypothesis that endogenous progestogen might have a hypertensive effect, as does exogenous progestogen. However, a second study designed to confirm this finding failed to do so, showing no cyclical change in the level of blood pressure. The subjects in the first study may have been subject to greater psychological stress when the measurements were made than were those in the second, a possibility supported by the large difference in pressure between the two studies. The discrepancy between the two sets of results could be explained if the effect possibly associated with progestogen levels in the retrospective study was due not to a hypertensive action per se but to a progestogen-related increased reaction to stress.

Adolescent↗

Adrenaline and noradrenaline excretion in placebo treated patients in the Medical Research Council Hypertension Trial and in matched normotensive controls.

The 24-h excretion of adrenaline and noradrenaline was measured in 268 untreated essential hypertensives and in 268 age- and sex-matched controls. No significant difference was found between the groups. However, in the control group alone, a multiple regression analysis showed a highly significant correlation between systolic blood pressure and both noradrenaline (P = 0.0006) and adrenaline (P = 0.0001). These results suggest that any role for elevated sympatho-adrenal activity in long-term blood pressure regulation is limited to the time before hypertension is established.

Adult↗

Urinary catecholamines in essential hypertension: results of 24-hour urine catecholamine analyses from patients in the Medical Research Council trial for mild hypertension and from matched controls.

Four consecutive 24-h urine samples were collected from 134 male and 134 female placebo-treated patients in the Medical Research Council Trial for Mild Hypertension. Similar samples were collected from age and sex-matched normotensive controls. On the fourth day noradrenaline excretion was 22.05 +/- 1.01 nmol/mmol creatinine in the hypertensives compared with 22.22 +/- 1.16 nmol/mmol creatinine in the controls. Adrenaline excretion on the same day was 6.13 +/- 0.33 nmol/mmol creatinine in the hypertensive subjects compared with 6.32 +/- 0.38 nmol/mmol creatinine in the controls. There was no significant difference for either catecholamine between the two groups. However, in the control group there was a highly significant correlation between excretion of adrenaline and systolic blood pressure (r = 0.218, p = 0.0004) and between noradrenaline excretion and systolic blood pressure (r = 0.200, p = 0.001). Catecholamine excretion and blood pressure were not significantly correlated in the hypertensive patients. There were no significant correlations in either group between catecholamine excretion and heart rate, caffeine intake, nicotine consumption or the Bortner self-assessment score of personality type. This study has found no evidence of elevated sympathoadrenal activity in mild hypertensives. The correlations in the control group may reflect the role of sympathoadrenal activity in acute fluctuations in blood pressure or may suggest that the level of blood pressure within the 'normal' range depends in part on the level of sympathoadrenal activity.

Adult↗